30 April 2015

Cream with nanoparticles will cure diabetic ulcers

Researchers at Northwestern University (Evanston, Illinois), working under the guidance of dermatologist Amy S. Paller and chemist Chad A. Mirkin, have developed a simple and at the same time high-tech cream that can help in the healing of chronic painful trophic ulcers developing on the legs of patients with diabetes mellitus. The active ingredient of the cream is spherical nucleic acids (SNA), which provide local blocking of the gene responsible for disrupting the wound healing process.

The incidence of type 2 diabetes is increasing worldwide, with more than 20% of patients with this disease suffering from chronic non-healing ulcers, in some cases leading to amputation of limbs.

In an earlier study, Dr. Paller and her colleagues demonstrated that the elimination of the GM3 synthase enzyme significantly increases the susceptibility of cells to growth factors and ensures normal wound healing even in diabetes mellitus. Together with Dr. Mirkin's laboratory, whose staff synthesized spherical nucleic acids selectively blocking the GM3 synthase gene, they developed and tested an experimental healing cream.

To do this, therapeutic synthetic nucleic acids were dissolved in the popular Aquaphor moisturizer, which was subsequently applied to the edges of ulcers formed in rats with a diet-induced model of diabetes mellitus. After four days, the condition of the ulcers of the animals of the experimental group was much better than the condition of the ulcers of the animals of the control groups. As a result, the ulcers of the treated animals healed within 12 days, whereas it took 18 days for the animals of the control group, that is, one and a half times more. The researchers also found that applying an experimental cream improved blood circulation in the area of damage.

The results obtained not only confirm the key role of GM3 synthase in the healing of diabetic ulcers, but also demonstrate the versatility of spherical nucleic acids, which are non-toxic to humans and theoretically can be used to affect any genetic target.

Each spherical nucleic acid is a gold nanoparticle with a diameter of 13 nanometers, covered with a dense layer of 40 double strands of RNA. A specially designed sequence of RNA chains ensures the blocking of the GM3 synthase gene.

According to Mirkin, such spherical structures are an ideal tool for delivering nucleic structures inside cells to regulate gene activity. They naturally penetrate into cells through interaction with phagocytic receptors that are not recognized by linear nucleic acids.

In one of the experiments, instead of spherical nucleic acids, the researchers added the same number of linear RNA chains with the same genetic sequence to the moisturizer. Applying such a cream to the edges of diabetic ulcers had no effect, the level of GM3 synthase did not decrease, and the condition of ulcers was similar to the condition of ulcers of control animal groups, which were applied with an empty moisturizer or cream containing spherical nucleic acids with a random genetic sequence.

The developers believe that the cream enriched with spherical nucleic acids can be used not only for the treatment, but also for the prevention of the development of diabetic ulcers, as well as to reduce the abnormal sensitivity of the skin of the feet of patients with diabetes mellitus. They are currently exploring this possibility.

The article by Pratik S. Randeria et al. siRNA-Based Spherical Nucleic Acids Reverse Impacted Wound Healing in Diabetic Mice by GM3 Synthase Knockdown is published in the journal Proceedings of the National Academy of Sciences.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Northwestern University:
Nanotech-Enabled Moisturizer Speeds Healing of Diabetic Skin Wounds.

30.04.2015

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